Extensive research has shown that nicotine functions as a primary reinforcer in both laboratory animals and humans and that the sensorimotor stimuli associated with nicotine delivery can act as conditioned reinforcers. However, several observations suggest that these two mechanisms (i.e., primary and conditioned reinforcement) cannot adequately explain smoking reinforcement. Nicotine is a relatively weak reinforcer when it is presented by itself (i.e., without any other stimuli), may not produce the discrete reinforcing neurobiological events that are an essential component of most primary reinforcement models, and interacts synergistically with nicotine-associated stimuli to reinforcer operant behavior. Recent preclinical research has uncovered a novel effect of nicotine that may help explain these observations and lead to a better understanding of the role of nicotine in smoking reinforcement. Nicotine greatly facilitates the reinforcing properties of other stimuli in a manner that is not dependent on the stimuli being temporally or causally related to nicotine. These findings suggest that nicotine may drive smoking behavior in two distinct ways - first, by acting as a primary reinforcer and consequently conveying conditioned reinforcing properties on nicotine-associated stimuli, and second, by directly potentiating other reinforcing properties of smoking (e.g., the conditioned reinforcement derived from smoking stimuli). The experiment proposed here tests this hypothesis by examining the effects of multiple doses of transdermal nicotine on the subjective, physiological, and reinforcing effects of nicotine-free cigarettes over multiple days of exposure in both a controlled laboratory setting and the natural environment. Given the grave health consequences of tobacco use, further understanding of the role of nicotine in smoking reinforcement is critically important. [unreadable] [unreadable]